title: Evaluation of the role of P-glycoprotein in ivermectin uptake by primary cultures of bovine brain microvessel endothelial cells.
abstract: The P-glycoprotein efflux system located on the apical membrane of brain capillary endothelial cells functions as part of the blood-brain barrier. In this study, primary cultures of bovine brain microvessel endothelial cells (BMECs) were investigated for the presence of a P-glycoprotein system and its contribution in regulating ivermectin distribution across the blood-brain barrier. Results of rhodamine 123 uptake studies with cyclosporin A and verapamil as substrates indicated that a functional efflux system was present on BMECs. Immunoblot analysis with the C219 monoclonal antibody to the product of the multidrug resistant member 1(MDR1) gene also confirmed the expression of MDR1 in the BMECs. Unbound ivermectin was shown to significantly increase the uptake of rhodamine 123 in BMECs, however, the drug only modestly enhanced the transcellular passage of rhodamine. The results of these studies affirmed that unbound ivermectin is an inhibitor of the MDR1 efflux system in BMECs.
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, School of Pharmacy, Lawrence 66047, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Rose
authors.forename: S L
authors.initials: SL
authors.lastname: Peckham
authors.forename: J L
authors.initials: JL
authors.lastname: Scism
authors.forename: K L
authors.initials: KL
authors.lastname: Audus
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D015151:Immunoblotting; D007559:Ivermectin / Q000378:metabolism* / Q000494:pharmacology; D008833:Microcirculation / Q000166:cytology / Q000378:metabolism; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005456:Fluorescent Dyes; D012235:Rhodamines; D020112:Rhodamine 123; D007559:Ivermectin